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Overview

This OpenSAFELY report was rapidly developed to support monitoring the ongoing roll-out of antivirals and neutralising monoclonal antibodies (nMABs) for the treatment of COVID-19, based on the population of 23.4m people registered with practices that use TPP SystmOne software. This report will be updated approximately weekly as new data arrives.

The code and data for this report can be found at the OpenSAFELY antibody-and-antiviral-deployment repository. The accompanying manuscript will be available shortly on MedRXiV (link to follow) and submitted for peer review.

Introduction

While vaccines remain the best strategy to prevent COVID-19, recent evidence suggests neutralising monoclonal antibodies (nMABs) or antivirals could potentially benefit certain vulnerable populations before or after exposure to SARS-CoV-2, such as the unvaccinated or recently vaccinated high-risk patients. On 16th December 2021, new COVID-19 Medicine Delivery Units (CMDUs) were launched across England, offering antiviral medicines and neutralising monoclonal antibodies (nMABs) as treatment to patients with COVID-19 at high risk of severe outcomes in outpatient clinics or their own home.

With the recent roll-out of nMABs and antivirals, there is an urgent need assess the coverage of these new treatments amongst these patients, such as factors of relevance in determining nMAB and antiviral treatment and the impact of nMAB and antiviral treatment in the community and hospital settings.

Using the OpenSAFELY platform we have developed and delivered a rapid, near real-time data-monitoring framework for the roll-out of antivirals and nMABs in England that can deliver detailed coverage reports in fine-grained clinical and demographic risk groups, using publicly auditable methods, using linked but pseudonymised patient-level NHS data in a highly secure Trusted Research Environment.

Full methods in code form can be found in the accompanying antibody-and-antiviral-deployment repository and are also described in our paper, linked above. Brief methods can be found at the end of the this report.

Results

Overall coverage of COVID-19 treatment

Between 11-Dec-2021 and 23-Feb-2022, a total of 50,730 non-hospitalised patients registered at a TPP practice in England were identified as potentially being eligible for receiving an antiviral or nMAB for treating COVID-19. Of the 50,730 potentially eligible patients, (15%) were classified into more than one high risk cohort (high risk cohort count range 1 - 6). The number of patients potentially eligible in each high risk cohort is described in Figure 1 and Table 1 below.

Of the 50,730 potentially eligible patients, 6,460 (13%) received treatment from a CMDU (Table 1, Figure 2);

  • Paxlovid: 110;
  • Sotrovimab: 3,610;
  • Remdesivir: 0;
  • Molnupiravir: 2,680;
  • Casirivimab: 50.


Figure 1 Cumulative total of potentially eligible patients for receiving an antiviral or nMABs for treating COVID-19 since 11th December 2021, stratified by high risk cohort. Patients are considered eligible on the date of their positive SARS-CoV-2 test. Note, patients can appear in more than one high risk group, and the overall number in each group is likely to be an overestimation due to including SARS-CoV-2 infection confirmed by either lateral flow or PCR test (where only PCR-confirmed infections should have been treated according to guidance in effect prior to 10th February 2022), and potentially including non-symptomatic patients.

**Figure 1 Cumulative total of potentially eligible patients for receiving an antiviral or nMABs for treating COVID-19 since 11th December 2021, stratified by high risk cohort.** Patients are considered eligible on the date of their positive SARS-CoV-2 test. Note, patients can appear in more than one high risk group, and the overall number in each group is likely to be an overestimation due to including SARS-CoV-2 infection confirmed by either lateral flow or PCR test (where only PCR-confirmed infections should have been treated according to guidance in effect prior to 10th February 2022), and potentially including non-symptomatic patients.


Figure 2 Cumulative total of patients who received an antiviral or nMAB for treating COVID-19 since 16th December 2021, stratified by (a) treatment type and (b) high risk cohorts. Shorter lines for Paxlovid and casirivimab reflect availability and guidance. Note, treated patients can appear in more than one high risk group.

**Figure 2 Cumulative total of patients who received an antiviral or nMAB for treating COVID-19 since 16th December 2021, stratified by (a) treatment type and (b) high risk cohorts.** Shorter lines for Paxlovid and casirivimab reflect availability and guidance. Note, treated patients can appear in more than one high risk group.


**(b)**

(b)


Table 1 Count and proportion of potentially eligible patients in OpenSAFELY-TPP who have received treatment for COVID-19 between 16th December 2021 23rd February 2022, broken down by high risk cohort and treatment type. Patient counts >5 are rounded to the nearest 10; as a result percentages may not add up to 100%.
Treated
Eligible
All
Paxlovid
Sotrovimab
Remdesivir
Molnupiravir
Casirivimab
High risk cohort Count Count % Count % Count % Count % Count % Count %
All 50730 6420 13 (12-13) 80 1 (1-2) 3600 56 (55-57) <5 2680 42 (41-43) 50 1 (1-1)
Immune-mediated inflammatory disorders 20390 3030 15 (14-15) 30 1 (1-1) 1720 57 (55-59) <5 1250 41 (40-43) 20 1 (0-1)
Primary immune deficiencies 9940 1190 12 (11-13) 20 2 (1-2) 620 52 (49-55) <5 540 45 (43-48) 10 1 (0-1)
Solid cancer 8370 950 11 (11-12) 10 1 (0-2) 550 58 (55-61) <5 380 40 (37-43) 10 1 (0-2)
Rare neurological conditions 5680 920 16 (15-17) 20 2 (1-3) 480 52 (49-55) <5 420 46 (42-49) 10 1 (0-2)
Haematological diseases and stem cell transplant recipients 4530 930 21 (19-22) 10 1 (0-2) 520 56 (53-59) <5 390 42 (39-45) 10 1 (0-2)
Solid organ transplant recipients 3490 860 25 (23-26) <5 560 65 (62-68) <5 290 34 (31-37) 10 1 (0-2)
Renal disease 3160 800 25 (24-27) <5 540 68 (64-71) <5 260 32 (29-36) 10 1 (0-2)
Liver disease 3130 320 10 (9-11) <5 170 53 (48-59) <5 140 44 (38-49) <5
Down’s syndrome 1090 150 14 (12-16) <5 50 33 (26-41) <5 100 67 (59-74) <5
Immunosuppression due to HIV or AIDS 330 190 58 (52-63) <5 70 37 (30-44) <5 120 63 (56-70) <5
* High risk cohorts are arranged in descending order, according to number of potentially eligible patients
All percentages (%) are caluclated with 95% confidence intervals

High risk patient cohorts

The proportion of potentially eligible patients receiving treatment varied over time and by high risk cohort (Figure 3).

Figure 3 Weekly proportion of eligible patients receiving an antiviral or nMAB for treating COVID-19 since 11th December 2021, stratified by high risk cohort

**Figure 3 Weekly proportion of eligible patients receiving an antiviral or nMAB for treating COVID-19 since 11th December 2021, stratified by high risk cohort**

Key demographic and clinical characteristics of treated patients

Table 2 shows the count and proportion of potentially eligible patients who received treatment for COVID-19 by 23-Feb-2022, broken down by demographic and clinical categories and by treatment type. The proportion treated varied by ethnicity, NHS Regions and by rurality. There was also lower coverage among care home residents, those with dementia, those with sickle cell disease, unvaccinated patients and in the most socioeconomically deprived areas. Patients who were housebound, or who had a severe mental illness also had a slightly reduced chance of being treated.

Table 2 Count and proportion of potentially eligible patients in OpenSAFELY-TPP who have received treatment for COVID-19 between 11th December 2021 and 23rd February 2022, broken down by demographic and clinical categories and by treatment type. Patient counts >5 are rounded to the nearest 10; as a result percentages may not add up to 100%.
Treated
Eligible
All
Paxlovid
Sotrovimab
Remdesivir
Molnupiravir
Group Variable Count Count % Count % Count % Count % Count %
Age band 12-29 5050 550 11 (10-12) 10 2 (1-3) 300 55 (50-59) <5 230 42 (38-46)
Age band 30-39 6470 990 15 (14-16) 10 1 (0-2) 570 58 (54-61) <5 390 39 (36-42)
Age band 40-49 8390 1320 16 (15-17) 20 2 (1-2) 750 57 (54-59) <5 530 40 (38-43)
Age band 50-59 10050 1450 14 (14-15) 40 3 (2-4) 820 57 (54-59) <5 580 40 (37-43)
Age band 60-69 8740 1130 13 (12-14) 20 2 (1-3) 640 57 (54-60) <5 460 41 (38-44)
Age band 70-79 7330 760 10 (10-11) 10 1 (1-2) 410 54 (50-57) <5 340 45 (41-48)
Age band 80+ 4700 270 6 (5-6) <5 110 41 (35-47) <5 150 56 (50-61)
Sex Female 28640 3810 13 (13-14) 70 2 (1-2) 2170 57 (55-59) <5 1550 41 (39-42)
Sex Male 22090 2650 12 (12-12) 40 2 (1-2) 1440 54 (52-56) <5 1130 43 (41-45)
Sex Unknown <5 <5 <5 <5 <5 <5
Ethnicity White 40570 5480 14 (13-14) 100 2 (1-2) 3090 56 (55-58) <5 2240 41 (40-42)
Ethnicity Asian or Asian British 2540 330 13 (12-14) <5 210 64 (58-69) <5 120 36 (31-42)
Ethnicity Black or Black British 2030 190 9 (8-11) <5 100 53 (46-60) <5 80 42 (35-49)
Ethnicity Mixed 670 80 12 (9-14) <5 40 50 (39-61) <5 40 50 (39-61)
Ethnicity Other ethnic groups 830 90 11 (9-13) <5 40 44 (34-55) <5 50 56 (45-66)
Ethnicity Unknown 4090 290 7 (6-8) 10 3 (1-6) 130 45 (39-51) <5 150 52 (46-57)
IMD 1 most deprived 10310 920 9 (8-9) 20 2 (1-3) 530 58 (54-61) <5 370 40 (37-43)
IMD 2 10000 1180 12 (11-12) 20 2 (1-2) 650 55 (52-58) <5 500 42 (40-45)
IMD 3 10340 1450 14 (13-15) 20 1 (1-2) 800 55 (53-58) <5 610 42 (40-45)
IMD 4 9720 1350 14 (13-15) 20 1 (1-2) 770 57 (54-60) <5 550 41 (38-43)
IMD 5 least deprived 8970 1380 15 (15-16) 30 2 (1-3) 760 55 (52-58) <5 580 42 (39-45)
IMD Unknown 1400 180 13 (11-15) <5 100 56 (48-63) <5 80 44 (37-52)
Rurality Urban - conurbation 13660 1370 10 (10-11) 20 1 (1-2) 770 56 (54-59) <5 580 42 (40-45)
Rurality Urban - city and town 26040 3470 13 (13-14) 70 2 (2-2) 1840 53 (51-55) <5 1520 44 (42-45)
Rurality Rural - town and fringe 5900 850 14 (14-15) 10 1 (0-2) 520 61 (58-64) <5 310 36 (33-40)
Rurality Rural - village and dispersed 3790 590 16 (14-17) 10 2 (1-3) 380 64 (61-68) <5 200 34 (30-38)
Rurality Unknown 1350 180 13 (12-15) <5 100 56 (48-63) <5 80 44 (37-52)
Region East Midlands 9050 1060 12 (11-12) 20 2 (1-3) 740 70 (67-73) <5 280 26 (24-29)
Region East of England 12000 2040 17 (16-18) 10 0 (0-1) 1110 54 (52-57) <5 890 44 (41-46)
Region London 3210 420 13 (12-14) 10 2 (1-4) 160 38 (33-43) <5 250 60 (55-64)
Region North East 2730 320 12 (11-13) <5 240 75 (70-80) <5 80 25 (20-30)
Region North West 5340 610 11 (11-12) 20 3 (2-5) 300 49 (45-53) <5 290 48 (44-52)
Region South East 3240 430 13 (12-14) 10 2 (1-4) 240 56 (51-61) <5 180 42 (37-47)
Region South West 5880 940 16 (15-17) 30 3 (2-4) 440 47 (44-50) <5 460 49 (46-52)
Region West Midlands 2080 250 12 (11-13) <5 200 80 (75-85) <5 50 20 (15-25)
Region Yorkshire and the Humber 7140 400 6 (5-6) 10 2 (1-4) 180 45 (40-50) <5 210 52 (48-57)
Region Unknown 70 10 14 (6-22) <5 0 0 (0-0) <5 <5
Autism Autism 300 40 13 (9-17) <5 20 50 (35-65) <5 30 75 (62-88)
Care home Care home 1700 60 4 (3-4) <5 10 17 (7-26) <5 50 83 (74-93)
Dementia Dementia 1230 50 4 (3-5) <5 10 20 (9-31) <5 30 60 (46-74)
Learning disability Learning disability 1310 170 13 (11-15) 0 0 (0-0) 60 35 (28-42) <5 100 59 (51-66)
Serious mental illness Serious mental illness 700 70 10 (8-12) <5 30 43 (31-54) <5 30 43 (31-54)
Housebound Housebound 1830 180 10 (8-11) <5 90 50 (43-57) <5 80 44 (37-52)
CEV CEV 26850 4570 17 (17-17) 70 2 (1-2) 2600 57 (55-58) <5 1860 41 (39-42)
Sickle cell disease Sickle cell disease 750 50 7 (5-8) <5 20 40 (26-54) <5 20 40 (26-54)
Vaccination status Un-vaccinated (declined) 790 30 4 (2-5) <5 20 67 (50-84) <5 10 33 (16-50)
Vaccination status Un-vaccinated 2310 120 5 (4-6) <5 60 50 (41-59) <5 60 50 (41-59)
Vaccination status One vaccination 1580 130 8 (7-10) <5 70 54 (45-62) <5 50 38 (30-47)
Vaccination status Two vaccinations 7330 520 7 (7-8) 10 2 (1-3) 280 54 (50-58) <5 220 42 (38-47)
Vaccination status Three or more vaccinations 38720 5660 15 (14-15) 100 2 (1-2) 3190 56 (55-58) <5 2340 41 (40-43)
* Due to not being used after December 2021, Casirivimab had been omitted from this table
* All percentages (%) are caluclated with 95% confidence intervals

Consistency with guidance

Of the 6,460 patients who received treatment for COVID-19 between 11-Dec-2021 and 23-Feb-2022, 1,255 patients were missing records needed to confirm eligibility; 2% did not have evidence of a positive SARS-CoV-2 test, 16% did not have a high risk cohort identified from their GP records alone, and 1% were discharged from hospital within 30 days prior to their positive test or treatment date, where COVID-19 was the primary diagnosis. There were also a small number of other potential inconsistencies with guidance for patients who received treatment, such as having a potential contraindication to the treatment given (Figure 3).

Figure 3 Breakdown of possible inconsistencies with guidance on eligibility/exclusion criteria in treated COVID-19 patients. Treatment eligibility window for Paxlovid, sotrovimab and molnupiravir was 5 days from positive SARS-CoV-2 test (used as a proxy for symptom onset date) and 7 days for remdesivir.

**Figure 3 Breakdown of possible inconsistencies with guidance on eligibility/exclusion criteria in treated COVID-19 patients.** Treatment eligibility window for Paxlovid, sotrovimab and molnupiravir was 5 days from positive SARS-CoV-2 test (used as a proxy for symptom onset date) and 7 days for remdesivir.

Time to treatment

Overall, of the 6,460 patients who received treatment, 94% did so within the respective treatment-specific eligibility window as estimated from test date (as symptom date is not consistently available) (Figure 4).

Figure 4 Time (number of days) between positive SARS-CoV-2 test and treatment for COVID-19, broken down by (a) treatment type and (b) high risk cohort.

**Figure 4 Time (number of days) between positive SARS-CoV-2 test and treatment for COVID-19, broken down by (a) treatment type and (b) high risk cohort.**




Methods

Full methods in code form can be found in the accompanying antibody-and-antiviral-deployment repository and are also described in our paper, linked above. Brief methods are given below.

Data sources

All data were analysed securely through OpenSAFELY-TPP https://opensafely.org which contains the full pseudonymised primary care records for all patients currently registered with general practices using TPP SystmOne software (approximately 23.4 million, 40% of the English population). Data were linked with accident and emergency (A&E) attendance and in-patient records from NHS Digital; national coronavirus testing records from the Second Generation Surveillance System (SGSS); and the “COVID-19 therapeutics dataset”, a patient-level dataset on antiviral and nMAB treatments from NHS England, derived from software used to notify NHS England of COVID-19 treatments.

Study population

Base population
  • Patients with either a positive SARS-CoV-2 test on or after 11th December 2021 (this is the earliest date that a patient could have tested positive and still been eligible for receiving treatment when they became available from CMDUs from 16th December 2021) or with a treatment record on or after 16th December 2021, who were also registered at the time of their test/treatment.
  • Patients aged under 12 or with an unknown date of birth were excluded.
Eligible patients

Where possible eligibility criteria were applied as per the Interim Clinical Commissioning Policy for non-hospitalised COVID-19 patients (NHSE, 28/01/2022) this included:

  • SARS-CoV-2 infection confirmed by a PCR or lateral flow test
  • being a member of a high risk cohort (determined by applying the detailed codelists and logic from NHS Digital as far as possible)

There were two main differences to the official criteria in our implementation. Firstly, prior to 10th February 2022, infection should have been confirmed by a PCR test, however this was then relaxed to include lateral flow tests. We were not able to always distinguish between lateral flow and PCR tests in all test records, and therefore included all positive SARS-CoV-2 test results. Secondly, having symptomatic COVID-19 was also an eligibility criteria: however due to difficulties in determining symptom status (i.e. it was only possible to determine whether a patient’s positive test had a “symptomatic” flag at the time of the test, but not whether symptoms developed later) we did not implement this requirement in our analysis; however we do address this in a separate sensitivity analysis, where we restricted the potentially eligible population to only those with a “symptomatic” flag associated with their positive SARS-CoV-2 test to determine its use as an indicator of being potentially asymptomatic.We also included patients in the eligible population if they were in the Treated cohort below.

Treated patients
  • Treatments and the date they were given were identified in the COVID-19 therapeutics dataset, restricted to those treated in the community (“non_hospitalised”)
  • Patients issued more than one treatment within two weeks of one another, or with an implausible treatment date (e.g. far in the future) were excluded

Key demographic and clinical characteristics

We classified treated patients by age group, sex, NHS region of their general practice and other key demographics including ethnicity and the level of deprivation. Deprivation was measured by Index of Multiple Deprivation (IMD), in quintiles, derived from the patient’s postcode at lower super output area level for a high degree of precision. Ethnicity was ascertained using 270 clinical codes grouped into broad categories White, Black or Black British, Asian or Asian British, Mixed, Other, and Unknown. Individuals with missing sex, ethnicity, IMD or region were included as “Unknown”. Treated patients were described according to whether they were in other groups of interest who are sometimes subject to variation in care, including autism, dementia, learning disability, serious mental illness, care home residents, and housebound. In addition we classified treated patients by their COVID-19 vaccination status (unvaccinated, unvaccinated with a record of declining vaccination, one vaccination, two vaccinations, or three or more).

Consistency with guidance

For patients who received treatment but who were not otherwise identified as potentially being eligible for treatment, we report which eligibility or exclusion criteria were not met according to the data available (i.e. no positive SARS-CoV-2 test result, or not identified as part of a high risk group). Where possible within available data, we also report other potential inconsistencies with guidance for patients who received treatment, such as where the high risk cohort identified within their records did not match the high risk cohort associated with their treatment.

We also assess consistency with treatment-specific criteria, such as patients having a recorded contraindication to the specific treatment given (e.g. adolescents treated with sotrovimab/remdesivir with weight under 40kg, Table S2), or patients treated outside the prescribed timescale, 5-7 days from symptom onset, depending on the treatment. As symptom onset date was not available, here we used positive SARS-CoV-2 test as a proxy to estimate the extent to which patients may or may not have been treated outside the guidance time window.

Descriptive statistics

We generated charts showing the cumulative number of potentially eligible and treated patients per week, stratified by high risk group, and also stratified by treatment type for treated patients. We used simple descriptive statistics to summarise the counts and proportions of potentially eligible patients treated, stratified by treatment type and either high risk cohort or clinical and demographic groups, and to describe potential inconsistencies with guidelines. Charts and results not presented in this manuscript are available online for inspection in the associated Github antibody-and-antiviral-deployment repository. Patient counts of 0-5 are shown as “<5” with remaining counts rounded to the nearest 10 to protect against small number differences in our routinely updating data. All percentages (%) are calculated with 95% confidence intervals (CI).

Codelists

Detailed information on compilation and sources for every individual codelist are available at https://www.opencodelists.org/.